Breast-conserving surgery, or lumpectomy, is the most common surgical procedure for patients diagnosed with an early stage of invasive breast cancer. Clearly defined tumor margins and complete surgical removal of tumors are critical for preventing local recurrence and increasing disease-free survival. Currently, there is no accurate method to identify tumor margins pre- or intra-operatively. About 20% to 30% of the patients who undergo lumpectomy require additional surgery to excise any remaining tumors due to the presence of positive tumor margins. To develop a sensitive approach for detecting tumor margins in breast tissues, we propose to engineer a tumor targeted nanoparticle imaging probe and to realize the intraoperative imaging using microelectromechanical systems (MEMS) based photoacoustic tomography (PAT). The objectives of this proposed study are: 1) To develop a MEMS based dual-frequency photoacoustic tomography system for intraoperative tumor imaging; 2) To validate and optimize the nanoprobe-MEMS-PAT system using phantom and in vivo experiments; and 3) To evaluate the efficacy of in vivo nanoprobe-MEMS-PAT guided resection of mouse mammary tumors. The development of a sensitive and high resolution miniaturized MEMS based intraoperative photoacoustic imaging system should have great potential for determining tumor margins during surgery, preventing tumor recurrence and therefore, increasing the survival rate of breast cancer patients.